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Particle‐by‐Particle In Situ Characterization of the Protein Corona via Real‐Time 3D Single‐Particle‐Tracking Spectroscopy **
Author(s) -
Tan Xiaochen,
Welsher Kevin
Publication year - 2021
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.202105741
Subject(s) - particle (ecology) , corona (planetary geology) , nanoparticle tracking analysis , chemistry , characterization (materials science) , particle size , nanoparticle , analytical chemistry (journal) , tracking (education) , spectroscopy , in situ , nanotechnology , materials science , chemical physics , chromatography , physics , organic chemistry , biochemistry , microvesicles , astrobiology , psychology , microrna , oceanography , pedagogy , quantum mechanics , venus , gene , geology
Nanoparticles (NPs) adsorb proteins when exposed to biological fluids, forming a dynamic protein corona that affects their fate in biological environments. A comprehensive understanding of the protein corona is lacking due to the inability of current techniques to precisely measure the full corona in situ at the single‐particle level. Herein, we introduce a 3D real‐time single‐particle tracking spectroscopy to “lock‐on” to single freely diffusing polystyrene NPs and probe their individual protein coronas, primarily using bovine serum albumin (BSA) as a model system. The fluorescence signals and diffusive motions of the tracked NPs enable quantification of the “hard corona” using mean‐squared displacement analysis. Critically, this method's particle‐by‐particle nature enabled a lock‐in‐type frequency filtering approach to extract the full protein corona, despite the typically confounding effect of high background signal from unbound proteins. From these results, the dynamic in situ full protein corona is observed to contain twice the number of proteins compared to the ex situ‐measured “hard” protein corona.